Acute Functional Adaptation to Nephron Loss: Micropuncture Studies

The renal and proximal tubule response to contralateral kidney exclusion was studied in a variety of circumstances. Recollection micropuncture studies were performed to assess the response to contralateral kidney clamping in the normal or a remnant kidney of the dog. Acute clamping of the contralateral kidney for a normal and unilateral remnant kidney resulted in marked reduction in proximal TF/P inulin ratios in the experimental kidney reflecting a 15 percent reduction in fluid reabsorption. Mean fractional excretion of sodium, potassium and water increased significantly in remnant kidney dogs but no significant change was observed in normal dogs except for potassium excretion. The marked reduction in proximal reabsorption occurred as soon as 5-15 minutes after contralateral kidney clamping and was compensated by distal reabsorption. Acute obstruction of the contralateral ureter results in a similar markedly reduced proximal tubular reabsorption. The reduction in proximal reabsorption induced by contralateral clamping occurred in the presence of reduced perfusion pressure and volume expansion and to some extent with renal denervation. When prostaglandin E₂ or acetycholine were infused prior to contralateral kidney clamping, proximal reabsorption remained at control levels and the contralateral clamping response was blocked. Similar blockade occurred after treatment with indomethacin. Acute reduction in nephron mass causes a marked depression of proximal tubular sodium and fluid absorption not obviously accounted for by hemodynamicphysical factors and humoral factors may be involved. The level of distal reabsorption to increased proximal delivery following contralateral clamping, determines the net urinary excretion.     

Long-Term Responses to Loss of Renal Mass: Tubular Changes: A Micropuncture Study of HCO3 Reabsorption by the Hypertrophied Proximal Tubule

In rats with renal failure produced by excision of one kidney and infarction of large portions of the other kidney, given a low calcium, high phosphorus diet for 2-3 weeks, GFR was reduced by 80 percent, the fractional excretion of sodium increased from 7 to 23 percent, that of bicarbonate from 16 to 23 percent and that of water from 4 to 13 percent. Single nephron GFR in the remaining nephrons was nearly doubled and end-proximal TF/P_In was depressed from 2.3 to 1.8, and proximal TF/P_HCO3 from 0.52 to 0.35, the latter figure corresponding to an increase of absolute proximal HCO₃ reabsorption from 1.7 to 3.5 nEq/min or from 2.8 to 3.2 Eq/L of single nephron glomerular filtrate. Acute parathyroidectomy had no influence on the fall of GFR or the rise of SNGFR in the remaining nephrons and failed to cause any significant changes in proximal tubular bicarbonate reabsorption. Parathyroidectomy, on the other hand, practically prevented the rise of the fractional excretion of sodium and of water and inverted the rise of the fractional excretion of bicarbonate to a fall. The data are interpreted to indicate that secondary hyperparathyroidism in renal failure impairs distal nephron bicarbonate and sodium reabsorption and, thus, contributes to the maintenance of sodium balance, but could possibly aggravate acidosis.     

Association of calcium and sodium handling in the rabbit nephron. A micropuncture study.

Two-phase recollection micropuncture experiments were performed on female New Zealand rabbits to investigate the effect of flow rate (volume-expansion) compared to reabsorptive rate (furosemide) on calcium and sodium handling along the nephron. Group 1 (n = 6) rabbits represented nonvolume-expanded animals. Each experiment was conducted with a control phase followed by a second phase of furosemide administration (1 mg/kg/min). Group 2 rabbits (n = 6) were initially volume-expanded to 3% body weight with modified Ringers. The fractional excretion of sodium and calcium in the control phase of group I and II was 3 +/- 1 and 22 +/- 6% and 4 +/- 1 and 26 +/- 2%, respectively. Fractional excretion of sodium, calcium and magnesium rose after furosemide administration. The effect of volume expansion on sodium, calcium and magnesium remaining in the proximal tubule was relatively modest and not affected by furosemide. Our distal micropuncture data reveal that volume expansion has a greater inhibitory effect on fluid reabsorption at a site beyond the proximal micropuncture site (group 1, 9 +/- 2%, group 2,22 +/- 2%). After furosemide infusion, the amount of electrolytes remaining rose similarly in both groups; however, additional sodium and calcium reabsorption did not occur in the volume-expanded group in the final segment of the nephron. These results indicate that calcium reabsorption by the cortical terminal segment of the rabbits is passive similar to that suggested by the in vitro perfused study since no additional calcium reabsorption is seen in the volume-expanded rabbit.     

Micropuncture study of the renal responses of the urodele amphibian Necturus maculosus to injections of arginine vasotocin and an anti-aldosterone compound.

1. Necturus maculosus kidney function has been examined using standard clearance techniques and renal tubular micropuncture methodology. 2. Throughout, cyanocobalamin (vitamin B12) has been used to monitor glomerular filtration rate (GFR) and tubular water movements. It was established that this substance was handled by the Necturus kidney in a similar manner to inulin. It can be readily analysed, together with renal electrolytes, by electron microprobe techniques. 3. Profiles of transtubular gradients (TF:P ratios) along the nephron were established for osmolarity, sodium, potassium, calcium and cobalt (of cyanocobalamin). 4. Ureteral urine is always hyposmotic with respect to plasma and the site of dilution of the plasma ultrafiltrate is within the distal segment. 5. Up to 30% of the filtrate is isosmotically reabsorbed along the proximal tubule; the tubular fluid:plasma ratio for osmolarity and sodium is around 1, and the TF:P for cobalt of cyanocobalamin is about 1.4 by the end of this segment. 6. The renal effects of the neurohypophysial hormone arginine vasotocin (AVT) and an aldosterone antagonist (SC14266; Soldactone) have been examined. 7. AVT was consistently antidiuretic causing both a decreased GFR and an enhanced distal tubular reabsorption of water. 8. SC14266 also increased distal tubular reabsorption of water. Such an effect differs from that found in higher vertebrates, and may indicate a "glucocorticoid-type" of renal action for aldosterone in amphibians.     

Long-Term Responses to Loss of Renal Mass: Pathophysiological Aspects: The Effects of Functional Adaptation of Residual Nephrons on the Urinary Excretion of Drugs

In patients with chronic renal failure due to glomerulonephritis, pyelonephritis or polycystic kidneys the urinary clearance of free chloramphenicol (C_CHL) was depressed proportionally to GFR (C_In). The ordinate intercept of the regression line of C_CHL on C_In, however, consistently was positive (+3 to +5 ml/min). The fractional excretion of chloramphenicol in renal failure increased from its normal value of 50 percent as an exponential function of the decrease of GFR, and as a linear function of the fractional excretion of water or of sodium. Dietary sodium restriction had no influence on C_CHL in the patients, while water diuresis, in normal subjects, enhanced the urinary excretion of chloramphenicol. The data suggest that chloramphenicol is reabsorbed by back-diffusion and that increases of the rate of flow of urine and tubular fluid prevent back-diffusion.     

Long-Term Responses to Loss of Renal Mass: Pathophysiological Aspects: Role of Solute Excretion in Prevention of Norepinephrine-Induced Acute Renal Failure

Infusion of 0.75 μ g/kgbw/min norepinephrine (NE), for 40 minutes, into one renal artery in anesthetized dogs, induced acute renal failure (ARF). Subsequently there was nearly complete reversal of function within 8 weeks. Isotonic saline volume expansion, or renal vasodilation plus diuresis by acetylcholine (into renal artery: 20 μg/min) did not protect against this type of ARF. Volume expansion with either 5 or 20 percent mannitol partly prevented the fall of GFR 3 hours after NE, this protection being correlated with the magnitude of the osmolar clearance at the time of the insult. IV furosemide (10 mg/kg + 10 mg/kg/h; fluid losses replaced) afforded an even better protection. Proximal tubular necrosis in the “protected” kidneys was as severe as in non-protected kidneys. Glomerular cell morphology (scanning electron microscopy) was not altered by the 40-minute NE infusions. Functional “protection” appeared to depend on solute diuresis at the time of insult.     

Renal effects of dopamine and ANP in high volume expanded rats

Both dopamine (DA) and atrial natriuretic peptide (ANP) have been postulated to exert similar effects on the kidney, participating in the regulation of body fluid and sodium homeostasis. In the present study, experiments were performed in anesthetized and isotonic sodium chloride volume expanded rats. After acute volume expansion at 15 % of body weight during 30 min, glomerular filtration rate, urine output, sodium excretion, fractional sodium excretion, proximal and distal sodium excretion and blood pressure were measured. In additional groups we administered ANP or haloperidol or the combination of both to volume expanded animals. Blockade of DA receptors with haloperidol, attenuated diuretic and natriuretic responses to volume load. Proximal sodium excretion was not modified by haloperidol in all experimental groups of rats. Reduction in distal tubular excretion was induced by haloperidol in saline infusion expanded rat but not in ANP treated expanded animals. In conclusion, when exaggerated volume expansion is provoked, both DA and ANP exert renal tubular events, but ANP have a major central role in the regulation of renal sodium handling.     

Characterization of biological properties of synthetic and biological leukotriene B3

The effect of micropuncture of the renal papilla through an intact ureter on urinary concetrating ability of rats was examined. Micropuncture of the renal papilla caused a fall in urine osmolality in the punctured kidney from 1718 ± 106 to 1035 ± 79 mosmol/kg·H₂O. In order to investigate the role of renal prostaglandins in this process, PGE₂ excretion was measured and found to increase from 63.4 ± 14.0 to 205.5 ± 57.1 pg/min. Urine osmolality and PGE₂ excretion from the contralateral kidney were not significantly altered. In animals given meclofenamate (2 mg/kg·hr), renal PGE₂ excretion was reduced to 22.3 ± 5.1 pg/min prior to micropuncture and it remained low at 8.9 ± 1.8pg/min after papillary micropuncture. Meclofenamate also blocked the fall in urine osmolality caused by micropuncture of the renal papilla, with urine osmolality averaging 1940 ± 122 before and 1782 ± 96 mosmol/kg·H₂O after the micropuncture. These results indicated that papillary micropuncture through an intact ureter increased renal PGE₂ excretion and that a rise in renal production of PGE₂ or some other prostanoid is associated with a fall in urine concentrating ability.     

Renal metabolism of substance P in the dog.

Substance P is a potent vasodilatory, diuretic, and natriuretic agent. Since subcellular fractions of the kidney rapidly inactivate substance P in vitro, the present study was designed to examine this observation $\text{in}$$\text{vivo}$ in anesthetized dogs. Arterial, renal venous, and urinary levels of immunoreactive substance P were determined by radioimmunoassay and were found to be 117±11, 128±12 and 659±104 pg/ml, respectively. The urinary and fractional excretion of immunoreactive substance P were 122±22 pg/min and 6.6±2.0%, respectively. When substance P was infused intravenously, the arterial and renal venous plasma levels of immunoreactive material increased whereas the urinary levels did not change. Infusions of 50 ng/kg/min of substance P significantly decreased mean arterial pressure, urinary volume, creatinine clearance as well as the urinary excretion, clearance, and fractional excretion of immunoreactive substance P. During intrarenal infusion of ¹²⁵I-(8-Tyr) substance P, high levels of radioactive material were found in the urine and renal venous plasma which failed to migrate on thin layer chromatography with intact ¹²⁵I-(8-Tyr) substance P. Thus under these conditions, intact substance P was not released from the kidney into the urine or renal venous blood, but instead circulating substance P was rapidly and completely metabolized, probably by both vascular and tubular elements of the kidney.     

Evaluation of the diuretic and urinary electrolyte effects of methanolic extract of Peganum harmala L. in Wistar albino rats

The use of traditional medicines as a diuretic agent has been increasing in recent years. The diuretic activity of a number of plant extracts used as diuretic agents in ethnomedicine has been confirmed in experimental animals. However, despite the widespread use of Peganum harmala in traditional medicine, there is a paucity of data supporting its use as a diuretic agent. Therefore, the present study aimed to envisage the true effect and magnitude of diuresis of methanolic extract of P. harmala (MEPH) in comparison with a well-known diuretic drug furosemide using Wistar albino rats. MEPH was administered orally in three different doses (150, 300 and 450 mg/kg) to experimentally dehydrated rats. Furosemide (10 mg/kg orally) was used as a reference drug. The diuretic effect of the MEPH was evaluated by measuring urine volume, urine pH, urinary electrolyte levels, natriuretic and saliuretic effects. The urine volume (in mL) measured at 5 h and 24 h and electrolyte excretion (Na⁺, K⁺, and Cl⁻) at 24 h duration were measured. The urine output and urinary electrolyte excretion were found to be significantly higher in rats treated with MEPH as compared to normal rats in a dose dependent manner (P < 0.05). The results of our study were comparable to furosemide drug. Based on observed results, we can recommend that P. harmala may be an effective diuretic, however, toxicity studies should be conducted before administration.     

Role of renal prostaglandins in the fall in urine osmolality after papillary micropuncture

The effect of micropuncture of the renal papilla through an intact ureter on urinary concetrating ability of rats was examined. Micropuncture of the renal papilla caused a fall in urine osmolality in the punctured kidney from 1718 ± 106 to 1035 ± 79 mosmol/kg·H₂O. In order to investigate the role of renal prostaglandins in this process, PGE₂ excretion was measured and found to increase from 63.4 ± 14.0 to 205.5 ± 57.1 pg/min. Urine osmolality and PGE₂ excretion from the contralateral kidney were not significantly altered. In animals given meclofenamate (2 mg/kg·hr), renal PGE₂ excretion was reduced to 22.3 ± 5.1 pg/min prior to micropuncture and it remained low at 8.9 ± 1.8pg/min after papillary micropuncture. Meclofenamate also blocked the fall in urine osmolality caused by micropuncture of the renal papilla, with urine osmolality averaging 1940 ± 122 before and 1782 ± 96 mosmol/kg·H₂O after the micropuncture. These results indicated that papillary micropuncture through an intact ureter increased renal PGE₂ excretion and that a rise in renal production of PGE₂ or some other prostanoid is associated with a fall in urine concentrating ability.     

Morphological and physiological studies of rat kidney cortex slices undergoing isosmotic swelling and its reversal: A possible mechanism for ouabain-resistant control of cell volume

Summary Slices of rat kidney cortex were induced to swell by preincubation at 1°C in an isotonic Ringer's solution, and their capacity to reverse swelling, by net extrusion of cellular water, was studied during subsequent incubation at 25°C. The recovery from swelling was prevented by the respiratory inhibitor, antimycin A. On the other hand, extrusion of water was little affected by ouabain. The extrusion of water continuing in the presence of ouabain (but not that in its absence) was significantly reduced when furosemide was added or when medium Cl^– was replaced by NO ₃ ^– , or I^–. There was substantial variability in the morphological appearance of cells within the cortical slices. Different segments of the nephron showed different structural changes during swelling and its reversal, the proximal tubules being most markedly affected. Proximal tubular cells of swollen slices showed disorganization of brush borders and expansion of their apical surfaces, and contained vesicles in their apical cytoplasm. Upon recovery at 25°C, the apical portions of these cells showed reversal of the expansion, but some apical vesicles remained. These vesicles were much more numerous after recovery in the presence of ouabain, but they were much reduced in numbers, or totally absent, when recovery took place in the presence of furosemide or absence of Cl^–, with or without ouabain. The vesicles seen in the presence of ouabain alone appeared to fuse with each other and with infoldings of the basolateral plasma membrane. Rather similar results were obtained with distal tubular cells in the slices. We suggest that volume regulation in the proximal and distal tubular cells proceeds by way of two mechanisms. The first consists of extrusion of water coupled to the ouabain-sensitive transport of Na⁺ and K⁺. The other proceeds by way of an ouabain-resistant entry of water into apical cytoplasmic vesicles, following furosemide-sensitive movements of Cl^– and Na⁺; the vesicles then expel their contents by exocytosis at the basolateral cell borders.     

Long-Term Responses to Loss of Renal Mass: Glomerular Changes: Compensatory Renal Hypertrophy in Dogs: Single Nephron Glomerular Filtration Rate

Kidney weight, length of superficial and juxtamedullary proximal tubules, glomerular diameter, kidney filtration rate and PAH clearance, sodium excretion and intrarenal distribution of filtration (with ¹⁴C-ferrocyanide) were measured in the remaining hypertrophic kidneys of dogs 10 days after unilateral nephrectomy. Whereas kidney weight increased to 75 percent of the original total renal mass, proximal tubule length and mean glomerular diameter remained unchanged. PAH and creatinine clearance, and absolute, but not fractional, sodium excretion, rose significantly. The ratio superficial/juxtamedullary filtration rate remained unchanged, indicating parallel increases of filtration in both cortical regions of hypertrophied kidneys.     

Synthetic, structural and solution speciation studies on binary Al(III)–(carboxy)phosphonate systems. Relevance to the neurotoxic potential of Al(III)

Efforts to delineate the interactions of neurotoxic Al(III) with low molecular mass substrates relevant to neurodegenerative processes, led to the investigation of the pH-specific synthetic chemistry of the binary Al(III)-[N-(phosphonomethyl) iminodiacetic acid] (Al-NTAP), Al(III)-[nitrilo-tris(methylene-phosphonic acid)] (Al-NTA3P), and Al(III)-[1-hydroxy ethylidene-1,1-diphosphonic acid] (Al-HEDP) systems, in correlation with solution speciation studies. Reaction of Al(NO₃)₃·9H₂O with NTAP at pH 7.0 and 4.0 afforded the new species (CH₆N₃)₄[Al₂(C₅H₆NPO₇)₂(OH)₂]·8H₂O (1) and (NH₄)₂[Al₂(C₅H₆NPO₇)₂(H₂O)₂]·4H₂O (2), while reaction of Al(NO₃)₃·9H₂O with NTA3P led to K₈[Al₂(C₃H₆NP₃O₉)₂(OH)₂]·20H₂O (3). Complexes 1–3 were characterized by elemental analysis, FT-IR, ¹³C, ³¹P, ¹H NMR (for 1–2 solid state and solution NMR where feasible), and X-ray crystallography. The structures of 1–3 reveal the presence of uniquely defined dinuclear complexes of octahedral Al(III) bound to fully deprotonated phosphonate ligands, water and hydroxo moieties. The aqueous solution speciation studies on the aforementioned binary systems project a clear picture of the binary Al(III)–(carboxy)phosphonate interactions and species under variable pH-conditions and specific Al(III):ligand stoichiometry. The concurrent solid state and solution work (a) exemplifies essential structural and chemical attributes of soluble aqueous species, reflecting well-defined interactions of Al(III) with phosphosubstrates and (b) strengthens the potential linkage of neurotoxic Al(III) chemical reactivity toward O,N-containing (carboxy)phosphate-rich cellular targets.     

Management of Hyperparathyroidism in Kidney Transplantation Candidates: A Need for Consensus

Objective: To assess the evolving standards of care for hyperparathyroidism in kidney transplant candidates.Methods: An 11-question, Institutional Review Board–approved survey was designed and reviewed by multiple institutions. The questionnaire was made available to the American Society of Transplantation's Kidney Pancreas Community of Practice membership via their online hub from April through July 2019.Results: Twenty percent (n = 41) of kidney transplant centers responded out of 202 programs in the United States. Forty-one percent (n = 17) of respondents believed medical literature supports the concept that a serum parathyroid hormone level greater than 800 pg/mL could endanger the survival of a transplanted kidney and therefore makes transplantation in an affected patient relatively or absolutely contraindicated. Sixty-six percent (n = 27) said they occasionally recommend parathyroidectomy for secondary hyperparathyroidism prior to transplantation, and 66% (n = 27) recommend parathyroidectomy after transplantation based on persistent, unsatisfactory posttransplantation parathyroid hormone levels. Forty-six percent (n = 19) prefer subtotal parathyroidectomy as their choice; 44% (n = 18) had no standard preference. Endocrine surgery and otolaryngology were the most common surgical specialties consulted to perform parathyroidectomy in kidney transplant candidates. The majority of respondents (71%, n = 29) do not involve endocrinologists in the management of kidney transplantation candidates.Conclusion: Our survey shows wide divergence of clinical practice in the area of surgical management of kidney transplantation candidates with hyperparathyroidism. We suggest that medical/surgical societies involved in the transplantation care spectrum convene a multidisciplinary group of experts to create a new section in the kidney transplantation guidelines addressing the collaborative management of parathyroid disease in transplantation candidates.Abbreviations: AACE = American Association of Clinical Endocrinologists; AAES = American Association of Endocrine Surgeons; AHNS = American Head and Neck Society; CKD = chronic kidney disease; CKD-MBD = chronic kidney disease–mineral and bone disorder; ESRD = end-stage renal disease; HPT = hyperparathyroidism; KDIGO = Kidney Disease Improving Global Outcomes; KT = kidney transplantation; KTC = kidney transplant candidate; PTH = parathyroid hormone; PTX = parathyroidectomy; US = ultrasonography     

Metformin: Nonglycemic Effects and Potential Novel Indications

Objective: Metformin is the most commonly prescribed drug for the treatment of type 2 diabetes because of its apparent robust effects in reducing cardiovascular risk. This review examines the current literature regarding the nonglycemic effects and potential novel indications for metformin.Methods: Review of the literature, with a focus on metformin use in Stage 3 chronic kidney disease (CKD-3) and heart failure (HF).Results: The United Kingdom Prospective Diabetes Study suggests that metformin reduces the risk of myocardial infarction, and more recent retrospective studies have shown an association between metformin use and a reduction in stroke, atrial fibrillation and all-cause mortality. The mechanism(s) explaining these putative benefits are not clear but may involve decreased energy intake (with attendant weight loss), improvement in lipids, and lowering of blood pressure; a literature review suggests that metformin lowers blood pressure when it is elevated, but not when it is normal. Metformin appears to be safe when given to patients with CKD-3. In addition, there is evidence that individuals with CKD-3, who are at increased cardiovascular risk, stand to benefit from metformin therapy. Lactic acidosis is an extremely remote and probably avoidable risk; measurement of plasma metformin levels and more frequent monitoring of renal function may be useful in selected patients with CKD-3 who are treated with metformin. Finally, there is evidence that metformin is safe in patients with HF; metformin therapy is associated with a reduction in newly incident HF and in HF mortality.Conclusion: Metformin has a dominant position in the treatment of type 2 diabetes that is deserved due to its favorable and robust effects on cardiovascular risk.Abbreviations:AMP = adenosine monophosphateBP = blood pressureCKD = chronic kidney diseaseCKD-3 = Stage 3 CKDeGFR = estimated glomerular filtration rateHDL = high-density lipoproteinHF = heart failureMAP = mean arterial pressuremVO₂ = myocardial oxygen consumptionT2DM = type 2 diabetes mellitusUKPDS = United Kingdom Prospective Diabetes Study     

Long-Term Responses to Loss of Renal Mass: Pathophysiological Aspects: The Influence of Age on the Response to Renal Parenchymal Loss

The effect of age on compensatory hypertrophy and functional adaptation to loss of 75 percent of renal mass was studied in canine puppies. In one group of animals the surgery was done between 1-5 days after birth and in another group, at two months of age. All animals were studied six weeks later. Shamoperated littermates served as controls. The newborn puppies in the experimental group were able to grow and maintain homeostasis as well as their controls, whereas the older experimental animals grew poorly and had significantly higher levels of plasma creatinine than their sham-operated counterparts (p < .05). The increase in mass of the remaining kidney was twice as much in the newborn as in the older dogs. Functional adaptation, as expressed by GFR, was nearly complete in the young, but reached only about 45 percent of controls in the older age group (p<.005). The intrarenal blood flow distribution was similar for experimental and control animals in both groups studied. There were, however, marked differences in the pattern of single glomerular perfusion rates: whereas in the older dogs the increase was confined to the deeper nephrons, in the newborn an increase occurred in all zones of the kidney. These studies demonstrate that compensation for massive loss of renal tissue is complete when the injury is sustained in the immediate postnatal period but only partial when it occurs later on in life. A loss in the adaptive capacity of the superficial nephrons appears to account for this age-related difference.     

1,1-Difluoroethyl-substituted triazolothienopyrimidines as inhibitors of a human urea transport protein (UT-B): New analogs and binding model

The kidney urea transport protein UT-B is an attractive target for the development of small-molecule inhibitors with a novel diuretic (‘urearetic’) action. Previously, two compounds in the triazolothienopyrimidine scaffold (1a and 1c) were reported as UT-B inhibitors. Compound 1c incorporates a 1,1-difluoroethyl group, which affords improved microsomal stability when compared to the corresponding ethyl-substituted compound 1a. Here, a small focused library (4a–4f) was developed around lead inhibitor 1c to investigate the requirement of an amidine-linked thiophene in the inhibitor scaffold. Two compounds (4a and 4b) with nanomolar inhibitory potency (IC₅₀ ≈ 40 nM) were synthesized. Computational docking of lead structure 1c and 4a–4f into a homology model of the UT-B cytoplasmic surface suggested binding with the core heterocycle buried deep into the hydrophobic pore region of the protein.     

Long-Term Responses to Loss of Renal Mass: Control Mechanisms: Glomerulotubular Dimensional Readjustments During Compensatory Renal Hypertrophy in the Hypothyroid Rat

Although growth of tubules is arrested and that of glomeruli retarded by hypothyroidism in rats, unilateral nephrectomy has been found to elicit a vigorous compensatory hypertrophy of the hypothyroid kidney. Microdissection and measurement of the dimensions of glomeruli and proximal convoluted tubules taken from the kidney removed first and from the hypertrophic contralateral organ removed two to three weeks later, disclosed a “normalization” of the typical glomerulotubular dimensional imbalance as a result of greater tubular than glomerular growth. A somewhat more striking but qualitatively identical response was observed in 9 euthyroid animals. Glomerular filtration rate and maximal glucose reabsorptive capacity (Tm_G) increased in both euthyroid and hypothyroid animals in accord with the structural shifts.     

Distal Renal Tubular Acidosis Due to Primary Hyperparathyroidism

ObjectiveTo present 4 cases of distal renal tubular acidosis (RTA) in patients with primary hyperparathyroidism (PHPT) and discuss their possible etiopathogenetic correlation.MethodsWe diagnosed distal RTA in 4 patients with symptomatic primary PHPT on the basis of the baseline biochemical variables and the results of the ammonium chloride loading test. Complete resolution of distal RTA was documented after surgical cure of PHPT by removal of a parathyroid adenoma.ResultsAll our patients presented with symptomatic bone disease and metabolic myopathy. One patient presented with recurrent renal stones. Inappropriately alkaline fasting urine (pH > 5.5) in association with a normal anion gap metabolic acidosis suggested the diagnosis of distal RTA. All cases were confirmed by an ammonium chloride loading test. Three patients responded to surgical cure of PHPT by normalization of the acid-base status.ConclusionHypercalciuria in PHPT can lead to nephrocalcinosis and renal tubular dysfunction, which manifests as distal RTA. Cure of distal RTA after surgical treatment of PHPT establishes PHPT as the primary cause of distal RTA in these cases. (Endocr Pract. 2008;14: 1133-1136)